The present invention relates to carboxylic acid amide derivatives and pharmaceutically acceptable acid addition salts thereof, being compounds which have useful analgesic and other pharmaceutical activity, and further relates to the preparation of such compounds.
In general, analgesic drugs acting on .kappa.-receptors do not show the side effects such as dependence, drug tolerance and respiratory inhibition shown by the morphine-like analgesic drugs acting on .mu.-receptors. Furthermore, analgesic drugs acting on .kappa.-receptors do not show cross resistance to morphine. Accordingly, the analgesic drugs acting on .kappa.-receptors are of considerable interest, because an agent which does not evince respiratory inhibition is useful for management of post-operative patients suffering from pain. Moreover, an agent without cross resistance is significant in clinical uses, for example, for patients suffering from cancer pain where tolerance to morphine and other antagonistic analgesic agents has occurred.
By way of example, European patent Specification 232612 published on Aug. 19, 1987 discloses azacyclic compounds which exhibit .kappa.-receptor agonism. The compounds are without the behavioural effects of morphine and morphine analogs, and are thus of potential therapeutic utility as analgesics. A small class of compounds within the generality of European patent Specification 232612 and said to have improved properties are disclosed in European patent Specification 260041 published on Mar. 16, 1988.